Blood–Brain Barrier Disruption

Abstract Delivery of therapeutic molecules into the central nervous system (CNS) is hampered by the blood–brain barrier (BBB). Various methods have been developed to allow passage of agents into the CNS, and translational studies in BBB research attempt to evaluate toxicity and efficacy of global CNS delivery of chemotherapeutics. Osmotic BBB disruption is a safe and effective means of delivering agents to the CNS when clinicians practice strict adherence to safety guidelines. The studies that have been conducted by participating BBB Consortium institutions have paved the way for safe delivery of agents to the CNS, with minimum local and systemic toxicities. Advances in the two-compartment model concept of pharmacokinetics suggest options for increasing therapeutic benefit and mitigating systemic toxicities for agents delivered to the CNS. The concept has proved beneficial in situations where drugs can be used in combination and with proper timing to act as chemoprotectants. Further development of BBB techniques will improve monitoring of therapeutic responses, as suggested by iron nanoparticles.